High levels of blood cholesterol is one of the major risk factors leading to atherosclerosis and cardiovascular diseases. Elevated cholesterol levels can be clinically lowered with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, collectively called statins. Statins have been showed in large clinical trial to effectively lower cholesterol blood levels. A vast amount of different statins exists today. High cholesterol values are very common in Europe and in USA and the use of statins to lower cholesterol values is increasing drastically. In EU-countries statin use increased from 1997 to 2002 by 30% on average.
Recent clinical data show that statin therapy is associated with adverse effects. The most prevalent and important adverse effect associated with statin therapy is myopathy. Myopathy is a collective term for various muscle related problems, such as muscle pain (myalgia), weakness and cramps (Paul D. Thompson et al, Am J Cardiol 2006, 97 [suppl]: 69C-76C). The exact mechanism for statin induced myopathy is still unclear. A recent study showed that clinically acceptable doses of atorvastatin and simvastatin resulted in lowered levels of plasma ubiquinone. Ubiquinone is a coenzyme that is involved in mithocondrial electron transport and is therefor involved in tissue energy metabolism. Statins such as atorvastatin and simvastatin clearly have an effect on skeletal muscle (Päivä et al, Clin Pharmacol Ther 2005; 78:60-8).
Metabolomics is a discipline dedicated to the systematic study of small molecules (i.e., metabolites) in cells, tissues, and biofluids. Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the amplified response of biological systems to genetic or environmental changes. Clinicians have relied for decades on a small part of the information contained in the metabolome, for example measuring glucose to monitor diabetes and measuring cholesterol for cardiovascular health. New sophisticated metabolomic analytical platforms and informatic tools have already been developed that afford extended and sensitive measurement of the metabolome.
Lipids are known to play an important role as structural components (e.g., cell membranes), energy storage components, and as signalling molecules. Lipids are broadly defined as hydrophobic or amphipathic small molecules that may originate entirely or in part by carbanion based condensation of thioesters, and/or by carbocation based condensation of isoprene units. Lipidomics can be considered as a sub-field of metabolomics which aims to elucidate the biological processes in the context of lipids by measuring and characterizing the extended lipid profiles at the molecular level (lipidomic profiles). Traditional clinical lipid measures quantify total amounts of triglycerides, cholesterol, or lipoproteins. However, serum lipid profile is more complex at the molecular level. Current lipidomics platforms enable quantitative characterization of 100 s of diverse lipid molecular species across multiple lipid classes such as sphingolipids, phospholipids, sterol esters, acylglycerols, sterols, bile acids, fatty acids, eicosanoids, and steroids.
Myopathy is today mainly diagnosed from the symptoms of the patient. Elevated creatine kinase (CK) levels can be used for testing patients with muscle symptoms. However, CK levels can be elevated due to other reasons such as exercise, and is not a reliable biomarker for statin induced myopathy. At the moment there is no diagnostic method or clinical test for diagnosing asymptomatic myopathy. Furthermore it is impossible to estimate the risk of a patient to develop myopathy when undergoing statin therapy. The present invention discloses a diagnostic method for determining the risk and early signs of statin induced myopathy.